Management of Non-Ventilated hospital acquired pneumonia

Non-ventilated hospital acquired pneumonia (NV-HAP) is defined as pneumonia that develops at least 48 h after hospital admission in the non-invasively ventilated patient. Guidance in the management of NV-HAP has historically used extrapolated research from the wider field of HAP, which includes patients with the separate clinical entity of ventilator associated pneumonia (VAP), or the field of community acquired pneumonia (CAP). However, NV-HAP is being increasingly recognised as a subtype of HAP owing to its high incidence, mortality, morbidity and health-economic burden. With a wide range of underlying causative organisms, the management approach focuses on initial broad-spectrum coverage of common bacterial pathogens. If microbiological results are available, targeted treatment can be started. Throughout all phases of treatment, supportive measures must also be considered. This includes the use of physiotherapy, oxygen and ventilatory support, fluid therapy and nutritional support. Research is ongoing into novel treatments, including new antimicrobials, nebulised therapies and monoclonal antibodies. Future research would benefit from a focussed approach that aims to standardise clinical and research definitions and treats NV-HAP as a separate entity to VAP. Collection of specific data would allow for the development of risk-stratification or severity tools which have been fundamental in improving the management of other pneumonia patients, for example, the use of CURB-65 in CAP. Review of commonplace supportive measures in the NV-HAP population would also be beneficial in view of the mostly frail co-morbid population affected

Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease

Startle disease is a rare, potentially fatal neuromotor disorder characterized by exaggerated startle reflexes and hypertonia in response to sudden unexpected auditory, visual or tactile stimuli. Mutations in the GlyR alpha(1) subunit gene (GLRA1) are the major cause of this disorder, since remarkably few individuals with mutations in the GlyR beta subunit gene (GLRB) have been found to date. Systematic DNA sequencing of GLRB in individuals with hyperekplexia revealed new missense mutations in GLRB, resulting in M177R, L285R and W310C substitutions. The recessive mutation M177R results in the insertion of a positively-charged residue into a hydrophobic pocket in the extracellular domain, resulting in an increased EC50 and decreased maximal responses of alpha(1)beta GlyRs. The de novo mutation L285R results in the insertion of a positively-charged side chain into the pore-lining 9' position. Mutations at this site are known to destabilize the channel closed state and produce spontaneously active channels. Consistent with this, we identified a leak conductance associated with spontaneous GlyR activity in cells expressing alpha(1)beta(L285R) GlyRs. Peak currents were also reduced for alpha(1)beta(L285R) GlyRs although glycine sensitivity was normal. W310C was predicted to interfere with hydrophobic side-chain stacking between M1, M2 and M3. We found that W310C had no effect on glycine sensitivity, but reduced maximal currents in alpha(1)beta GlyRs in both homozygous (alpha(1)beta(W310C)) and heterozygous (alpha(1)beta beta(W310C)) stoichiometries. Since mild startle symptoms were reported in W310C carriers, this may represent an example of incomplete dominance in startle disease, providing a potential genetic explanation for the 'minor' form of hyperekplexia. (C) 2012 Elsevier Inc. All rights reserved